Authors: J. Jenkins, K. Pant, J. Hood and S. Sundaram
Affilation: CFD Research Corporation, United States
Pages: 599 - 602
Keywords: nanoparticle, toxicity, multiscale, cellular, organ
Multiscale simulation of the toxic physiological effects of short and long term exposure to nanoparticles (NP) requires a unified quantitative understanding of NP deposition, partitioning of NP within the body (lung, liver, spleen, and brain), and inflammatory cellular response (Figure 1). Accurate prediction of the amount of internal and external deposition on the body (lung, skin, sinuses, eyes, etc.) is critical to setting the NP “dose”. For example, NP deposition in the lung is site-specific and depends, among other factors, upon the aerodynamic size, electrostatic charge distributions and gravitational forces (ex. space exploration) (Donaldson, 2005). Once inhaled, NPs can reach the sensitive alveolar regions and stay for long times, resulting in impaired cardio-vascular function (Peters, 2004). Given the dose, models describing cellular response upon NP contact can be used to determine the level of inflammation (Figure 2a). Cellular NP toxicity is primarily due to the generation of reactive oxygen species (ROS) through a series of complex cyclical intracellular chemical reactions that result in the production of the superoxide and hydroxyl ions (Figure 2b). Currently, there are no modeling platforms that enable the prediction of the multiscale physiological toxic response to NP exposure.<br>In response to this challenge, we propose to develop a CFD-driven Physiologically-based Pharmacokinetic model (CFD-PBPK) to assess the deposition of NP on humans.